The Human Bone Cell Production Core of the UAB Core Center for Basic Skeletal Research (CCBSR) provides human osteoblast .progenitor cells and human ostepclast-like cells. Through the P30 support mechanism, services are provided at no cost to the UAB CCBSR pilot project investigators and markedly reduced costs to other UAB CCBSR investigators. The centralization of the production of human bone cells ensures cost-effectiveness and improves the overall quality of the human bone cell preparations, which is ensured by adherence to a quality assurance plan that includes testing of the differentiation potential of the cells, and the provision of pre-tested sera and growth factors. In response to demand, the Core now provides murine cells and, in this-competitive renewal, proposes to provide siRNA gene expression reagents and techniques. This will reduce developmental and production costs, while improving the overall quality of the reagents. A key element of the Core is educational support dnd activities that enable investigators to utilize human bone cells in their research efforts. The Core has proven invaluable in improving the productivity of investigators in the area of basic bone biology research, having supported more than 100 projects that have resulted in 59 publications to date. Most of these projects have been instigated by CCBSR members and all of the pilot and feasibility project investigators have used the core. To date the Core has proven invaluable in supporting innovative research in the areas of bone cell differentiation and function, micrdgravity and druginduced bone loss, the bone loss associated with rheumatoid arthritis, and cancer-associated alterations in bone cells. Notably, it has supported truly interdisciplinary, innovative research in the areas of the implant biology and the development of gene therapy strategies. The efforts of this Core are closely coordinated with the efforts of the Histomorphometry and Molecular Analysis Core and the proposed Small Animal Bone Phenotyping Core, with several investigators utilizing all three of these Cores in the course of their ongoing studies. The proposed Specific Aims are: Specific Aim 1: Preparation and purification of human mesenchymal stem cells. Specific Aim 2: Preparation of human and mouse osteoclasts. Specific Aim 3: Development of a retrovirus-based siRNA approach for knock down of gene expression in osteoclast precursors or mature osteoclasts.